tRNA synthetase mutants of Escherichia coli K-12 are resistant to the gyrase inhibitor novobiocin

In previous studies we demonstrated that mutations in the genes cysB, cysE, and cls (nov) affect resistance of Escherichia coil to novobiocin (J. Rako njac, M. Milic, and D. J. Savic, Mel. Gen. Genet. 228:307-311, 1991; R Ivan isevic, M. Milic, D. Ajdic, J. Rakonjac, and D. J. Savic, J. Bacteriol. 177 :1766-1771, 1995). In this work we expand this list with mutations in rpoN (the gene for RNA polymerase subunit sigma(54)) and the tRNA synthetase gen es alaS, argS, ileS, and leuS. Similarly to resistance to the penicillin an tibiotic mecillinam, resistance to novobiocin of tRNA synthetase mutants ap pears to depend upon the ReIA-mediated stringent response. However, at this point the overlapping pathways of mecillinam and novobiocin resistance div erge. Under conditions of stringent response induction, either by the prese nce of tRNA synthetase mutations or by constitutive production of RelA prot ein, inactivation of the cls gene diminishes resistance to novobiocin but n ot to mecillinam.